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ABSTRACT: Type 1 diabetes mellitus increases the risk for sudden unexplained death, generating concern that diabetes processes and/or treatments underlie these deaths. Young (< 50 years) and otherwise healthy patients who are found dead in bed have been classified as experiencing 'dead-in-bed' syndrome.
We thus identified all unwitnessed deaths in two related registries (the Children's Hospital of Pittsburgh and Allegheny County) yielding 1319 persons with childhood-onset (age < 18 years) Type 1 diabetes diagnosed between 1965 and 1979. Cause of death was determined by a Mortality Classification Committee (MCC) of at least two physician epidemiologists, based on the death certificate and additional records surrounding the death.
Of the 329 participants who had died, the Mortality Classification Committee has so far reviewed and assigned a final cause of death to 255 (78%). Nineteen (8%) of these were sudden unexplained deaths (13 male) and seven met dead-in-bed criteria. The Mortality Classification Committee adjudicated cause of death in the seven dead-in-bed persons as: diabetic coma (n =4), unknown (n=2) and cardiomyopathy (n=1, found on autopsy). The three dead-in-bed individuals who participated in a clinical study had higher HbA(1c) , lower BMI and higher daily insulin dose compared with both those dying from other causes and those surviving.
Sudden unexplained death in Type 1 diabetes seems to be increased 10-fold and associated with male sex, while dead-in-bed individuals have a high HbA(1c) and insulin dose and low BMI. Although sample size is too small for definitive conclusions, these results suggest specific sex and metabolic factors predispose to sudden unexplained death and dead-in-bed death.
Diabetic Medicine 03/2011; 28(3):293-300. · 2.90 Impact Factor
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ABSTRACT: To complete a comparative analysis of studies that have examined the relationship between glycaemia and cardiovascular disease (CVD)/coronary artery disease (CAD) and perform a prospective analysis of the effect of change in glycosylated Hb level on CAD risk in the Pittsburgh Epidemiology of Diabetes Complications Study (EDC) of childhood-onset type 1 diabetes mellitus (n = 469) over 16 years of two yearly follow-up.
Measured values for HbA(1) and HbA(1c) from the EDC were converted to the DCCT-standard HbA(1c) for change analyses and the change in HbA(1c) was calculated (final HbA(1c) minus baseline HbA(1c)). CAD was defined as EDC-diagnosed angina, myocardial infarction, ischaemia, revascularisation or fatal CAD after medical record review.
The comparative analysis suggested that glycaemia may have a stronger effect on CAD in patients without, than in those with, albuminuria. In EDC, the change in HbA(1c) differed significantly between CAD cases (+0.62 +/- 1.8%) and non-cases (-0.09 +/- 1.9%) and was an independent predictor of CAD.
Discrepant study results regarding the relationship of glycaemia with CVD/CAD may, in part, be related to the prevalence of renal disease. Measures of HbA(1c) change over time show a stronger association with CAD than baseline values.
Diabetologia 12/2007; 50(11):2280-8. · 6.81 Impact Factor
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Advances in experimental medicine and biology 02/2002; 503:133-40. · 1.09 Impact Factor
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ABSTRACT: Most Caucasians with Type I (insulin-dependent) diabetes mellitus develop an autoimmune form of diabetes known as Type IA diabetes, based on the presence of humoral responses to islet autoantigens. Alleles at the HLA locus account for the strongest susceptibility to this form of diabetes, which requires insulin therapy. Because a number of patients who develop insulin-requiring diabetes are islet autoantibody negative, the HLA class II haplotypes, DQA1*0501-DQB1*0201 and DQA1*0301-DQB1*0302, were evaluated to assess whether they are an independent risk factor for progression to insulin requirement in first-degree relatives of Type I diabetic patients.
Both HLA-DQ genotyping and islet cell autoantibody assessment (insulin, GAD65, IA-2 autoantibodies and cytoplasmic islet cell antibodies) were evaluated prospectively in 74 relatives of Type I diabetic patients who developed diabetes treated with insulin (prediabetics) and in 426 control subjects who did not develop insulin-requiring diabetes. Based on the presence of DQA1*0501-DQB1*0201 and/or DQA1*0301-DQB1*0302, the number of HLA-DQ high-risk haplotypes was assigned as 0, 1 or 2.
A higher prevalence of 2 HLA-DQ high-risk haplotypes was present in seronegative prediabetic subjects as compared to non-diabetic autoantibody negative first-degree relatives (33.3 % vs 10.1 % respectively; p < 0.05). Moreover, in seronegative relatives who developed insulin-requiring diabetes, the presence of 2 HLA-DQ high-risk haplotypes conferred an increased cumulative risk of developing insulin requirement of 27 % at 12.5 years of follow-up, compared to a risk of 6 % for non-diabetic relatives who were antibody-negative and had 0 or 1 HLA-DQ high-risk haplotypes (Log rank p = 0.01).
These data provide evidence for a phenotype, which is associated with the absence of conventional islet autoantibodies at initial screening, while usually remaining seronegative, and the presence of 2 HLA-DQ high-risk haplotypes with progression to clinical Type I diabetes after a prolonged follow-up. Given the fact that in humans the highest risk-conferring locus associated and linked to the disease is the HLA cluster, and that HLA-DQ molecules play a key role in the development of autoimmune diabetes, our observations imply that as yet unidentified immunologic abnormalities could well exist in seronegative relatives at risk of developing clinical diabetes and carrying 2 HLA-DQ high-risk haplotypes.
Diabetologia 02/2002; 45(1):66-76. · 6.81 Impact Factor
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ABSTRACT: Subjects with type 1 diabetes are at high risk for many long-term complications, including early mortality and coronary artery disease (CAD). Few data are available on which to base goal levels for two major risk factors, namely blood pressure and lipid/lipoproteins. The objective of this study was to determine at which levels of LDL and HDL cholesterol, triglycerides, and blood pressure the relative risks of type 1 diabetic complications increase significantly.
Observational prospective study of 589 patients with childhood-onset type 1 diabetes (<17 years) aged > or =18 years at baseline; 10-year incidence of mortality, CAD, lower-extremity arterial disease, proliferative retinopathy, distal symmetric polyneuropathy, and overt nephropathy. Relative risks were determined using traditional groupings of blood pressure and lipid/lipoproteins, measured at baseline, using the lowest groupings (<100 mg/dl [2.6 mmol/l] LDL cholesterol, <45 mg/dl [1.1 mmol/l] HDL cholesterol, <100 mg/dl [1.1 mmol/l] triglycerides, <110 mmHg systolic blood pressure, and <80 mmHg diastolic blood pressure) as reference. Adjustments for age, sex, and glycemic control were examined.
Driven mainly by strong relationships (RR range 1.8-12.1) with mortality, CAD, and overt nephropathy, suggested goal levels are as follows: LDL cholesterol <100 mg/dl (2.6 mmol/l), HDL cholesterol >45 mg/dl (1.1 mmol/l), triglycerides <150 mg/dl (1.7 mmol/l), systolic blood pressure <120 mmHg, and diastolic blood pressure <80 mmHG: Age, sex, and glycemic control had little influence on these goals.
Although observational in nature, these data strongly support the case for vigorous control of lipid levels and blood pressure in patients with type 1 diabetes.
Diabetes Care 06/2001; 24(6):1053-9. · 8.09 Impact Factor
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S Winer,
I Astsaturov,
R K Cheung,
K Schrade,
L Gunaratnam,
D D Wood,
M A Moscarello,
P O'Connor,
C McKerlie, D J Becker,
H M Dosch
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ABSTRACT: Multiple sclerosis (MS) is a chronic autoimmune disease triggered by unknown environmental factors in genetically susceptible hosts. MS risk was linked to high rates of cow milk protein (CMP) consumption, reminiscent of a similar association in autoimmune diabetes. A recent rodent study showed that immune responses to the CMP, butyrophilin, can lead to encephalitis through antigenic mimicry with myelin oligodendrocyte glycoprotein. In this study, we show abnormal T cell immunity to several other CMPs in MS patients comparable to that in diabetics. Limited epitope mapping with the milk protein BSA identified one specific epitope, BSA(193), which was targeted by most MS but not diabetes patients. BSA(193) was encephalitogenic in SJL/J mice subjected to a standard protocol for the induction of experimental autoimmune encephalitis. These data extend the possible, immunological basis for the association of MS risk, CMP, and CNS autoimmunity. To pinpoint the same peptide, BSA(193), in encephalitis-prone humans and rodents may imply a common endogenous ligand, targeted through antigenic mimicry.
The Journal of Immunology 05/2001; 166(7):4751-6. · 5.79 Impact Factor
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Pediatric Diabetes 04/2001; 2(1):2-11. · 2.16 Impact Factor
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S Winer,
I Astsaturov,
R Cheung,
L Gunaratnam,
V Kubiak,
M A Cortez,
M Moscarello,
P W O'Connor,
C McKerlie, D J Becker,
H M Dosch
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ABSTRACT: Type I diabetes and multiple sclerosis (MS) are distinct autoimmune diseases where T cells target either islet or CNS self-proteins. Unexpectedly, we found that autoreactive T cells in diabetic patients, relatives with high diabetes risk, nonobese diabetic (NOD) mice, and MS patients routinely target classical islet as well as CNS autoantigens. The pathogenic potential of CNS autoreactivity was testable in NOD mice. Pertussis holotoxin, without additional Ags or adjuvants, allowed development of an NOD mouse-specific, autoimmune encephalitis with variable primary-progressive, monophasic, and relapsing-remitting courses. T cells from diabetic donors transferred CNS disease to pertussis toxin-pretreated NOD.scid mice, with accumulation of CD3/IFN-gamma transcripts in the brain. Diabetes and MS appear more closely related than previously perceived. NOD mouse-specific, autoimmune encephalitis provides a new MS model to identify factors that determine alternative disease outcomes in hosts with similar autoreactive T cell repertoires.
The Journal of Immunology 03/2001; 166(4):2831-41. · 5.79 Impact Factor
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S Winer,
L Gunaratnam,
I Astsatourov,
R K Cheung,
V Kubiak,
W Karges,
D Hammond-McKibben,
R Gaedigk,
D Graziano,
M Trucco, D J Becker,
H M Dosch
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ABSTRACT: Cross-reactive T cells that recognize both Tep69 (dominant nonobese diabetic (NOD) T cell epitope in ICA69 (islet cell autoantigen of 69 kDa)) and ABBOS (dominant NOD T cell epitope in BSA) are routinely generated during human and NOD mouse prediabetes. Here we analyzed how systemic administration of these mimicry peptides affects progressive autoimmunity in adoptively transferred and cyclophosphamide-accelerated NOD mouse diabetes. These models were chosen to approximate mid to late stage prediabetes, the typical status of probands in human intervention trials. Unexpectedly, high dose (100 microg) i.v. ABBOS prevented, while Tep69 exacerbated, disease in both study models. Peptide effects required cognate recognition of endogenous self-Ag, because both treatments were ineffective in ICA69null NOD congenic mice adoptively transferred with wild-type, diabetic splenocytes. The affinity of ABBOS for NOD I-A(g7) was orders of magnitude higher than that of Tep69. This explained 1) the expansion of the mimicry T cell pool following i.v. Tep69, 2) the long-term unresponsiveness of these cells after i.v. ABBOS, and 3) precipitation of the disease after low dose i.v. ABBOS. Disease precipitation and prevention in mid to late stage prediabetes are thus governed by affinity profiles and doses of therapeutic peptides. ABBOS or ABBOS analogues with even higher MHC affinity may be candidates for experimental intervention strategies in human prediabetes, but the dose translation from NOD mice to humans requires caution.
The Journal of Immunology 11/2000; 165(7):4086-94. · 5.79 Impact Factor
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ABSTRACT: We studied the relationship of coronary artery calcification (CAC), a marker of coronary atherosclerosis, with prevalent clinical coronary artery disease (CAD) and established cardiovascular disease (CVD) risk factors in a type 1 diabetic population. At the 10-year follow-up examination of the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study cohort, 302 adults (mean age 38.1 +/- 7.8 years) received electron beam tomography (EBT) scanning of the heart and a clinical examination. Clinical CAD was defined as a confirmed history of myocardial infarction (MI), angiographic stenosis > or =50%, Pittsburgh EDC Study physician-diagnosed angina, or ischemic electrocardiogram (ECG). CAC correlated with most CVD risk factors. CAC had 84 and 71% sensitivity for clinical CAD in men and women, respectively, and 100% sensitivity for MI or obstructive CAD. A CACS cut point of 400 was the most efficient coronary calcium correlate of CAD. In subjects with angina only, CAC sensitivity was 83% in men and 46% in women. In logistic regression, CAC, ECG R-R variation, peripheral vascular disease, and Beck Depression Inventory independently correlated with prevalent CAD in men and overall. Except for CAC, the same variables independently correlated with CAD in women, and age also entered the model. CAC was an independent correlate of MI or obstructive CAD in both sexes and was the strongest independent correlate in men, but CAC was not independently associated with angina and ischemic ECG in either sex. It is concluded that EBT-detected CAC is strongly correlated with CAD in type 1 diabetes-particularly in men.
Diabetes 09/2000; 49(9):1571-8. · 8.29 Impact Factor
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ABSTRACT: Hypoglycemia is the most common acute complication in insulin-treated type 1 diabetic patients. Most surveys have demonstrated that the tighter the glycemic control, and the younger the patient, the greater the frequency of both mild and severe hypoglycemia. However, people in poor metabolic control, with high glycosylated hemoglobin levels, are not protected from experiencing severe hypoglycemia. Focusing on the pediatric population, we review new or controversial issues surrounding the prevalence of hypoglycemia, its causes, its consequences and preventive strategies, and discuss possible mechanisms underlying the variability of responses to hypoglycemia.
Trends in Endocrinology and Metabolism 08/2000; 11(5):198-202. · 8.11 Impact Factor
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A L Rosenbloom,
D A Schatz,
J P Krischer,
J S Skyler, D J Becker,
R E Laporte,
I Libman,
M Pietropaolo,
H M Dosch,
L Finberg,
A Muir,
W V Tamborlane,
M Grey,
J H Silverstein,
J I Malone
Journal of Clinical Endocrinology & Metabolism 03/2000; 85(2):494-522. · 6.50 Impact Factor
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ABSTRACT: In the Type 1 diabetes population, coronary heart disease (CHD) and lower-extremity arterial disease (LEAD) are the two common macrovascular complications leading to early mortality and morbidity. However, it is not clear if these two complications share the same risk factors. The Pittsburgh Epidemiology of Diabetes Complications (EDC) Study prospectively examined and compared the risk factors for LEAD and CHD (including CHD morbidity and mortality). EDC subjects (332 men and 325 women), all diagnosed at Children's Hospital of Pittsburgh between 1950 and 1980, were first examined at baseline (1986-1988), and then biennially, for diabetes complications and their risk factors. Data used in the current analysis were from the first 6 years of follow-up, 98% provided at least some follow-up data for these analyses. CHD was defined as the presence of angina (diagnosed by the EDC examining physician) or a history of confirmed myocardial infarction or CHD death. An ankle-to-arm ratio of less than 0.9 at rest was considered to be evidence of LEAD. Among 635 subjects without CHD at baseline, 57 developed CHD (1.69/100 person-years), and among 579 without LEAD at baseline, 70 developed LEAD (2.31/100 person-years). CHD incidence rate was slightly higher in males, while LEAD incidence rate was slightly higher in females. Compared to non-incident cases, subjects who developed either complication were older, had a longer diabetes duration, higher LDL and total cholesterol, and were more likely to be hypertensive. In multivariate analyses, hypertension, low HDL cholesterol level, high white cell count, depression, and nephropathy were the independent risk factors for CHD (including morbidity and mortality). For LEAD, higher HbA1 level, higher LDL cholesterol level and smoking were the important contributing factors. In conclusion, the risk factor patterns differ between the two vascular complications. Glycemic control does not predict CHD overall but does predict LEAD, while hypertension and inflammatory markers are more closely related to CHD than to LEAD.
Atherosclerosis 02/2000; 148(1):159-69. · 3.79 Impact Factor
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ABSTRACT: An anergic phenotype has been observed in nonobese diabetic (NOD) mice and some autoreactive T cells from patients with type I diabetes. To better understand this phenomenon, we measured T cell proliferative responses to 10 diabetes-associated and up to 9 control Ags/peptides in 148 new diabetic children, 51 age- and MHC (DQ)-matched siblings (sibs), 31 patients with longstanding diabetes, and 40 healthy controls. Most (78-91%) patient and sib responses to glutamate decarboxylase of 65 kDa (GAD65), islet cell cytoplasmic autoantibody (ICA) 69, diabetes-associated T cell epitopes in ICA69 (Tep69), and heat shock protein (Hsp) 60 involved anergic T cells that required exogenous IL-2 to proliferate. Responses to proinsulin, IA-2 (and tetanus toxoid) required no IL-2 and generated sufficient cytokine to rescue anergic T cell responses. Most new patients (85%) had autoreactive T cells, three quarters targeting more than half of the diabetes Ags. Only 7.8% of the sibs and none of the controls had such multiple T cell autoreactivities, which thus characterize overt disease. Multiple anergic and nonanergic T cell autoreactivities were sustained during 2 yr follow-up after onset and in patients with longstanding (3-26 yr) diabetes. Activated patient T cells survived severe IL-2 deprivation, requiring 20-100 times less IL-2 than normal T cells to escape apoptosis. Diabetic T cell anergy thus persists for decades and is Ag and host specific but not related to disease course. Rescue by IL-2 from bystander T cells and high resistance to apoptosis may contribute to this persistence. These data explain some of the difficulties in the routine detection of disease-associated T cells, and they emphasize challenges for immunotherapy and islet transplantation.
The Journal of Immunology 01/2000; 163(12):6933-40. · 5.79 Impact Factor
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ABSTRACT: This article examines the relationship between hypoglycemia and brain function in children with type 1 diabetes. Hypoglycemic episodes occurring in the first 5 years of life may permanently disrupt cognitive function in a subset of children with diabetes, and a single acute episode of hypoglycemia may produce a transient reduction in mental efficiency, alter the electroencephalogram, and increase regional cerebral blood flow. Because iatrogenic development of hypoglycemic unawareness and autonomic failure are the most likely mediators of moderately severe hypoglycemia, medical management efforts should be directed at the prevention of frequently recurring, mild hypoglycemia.
Endocrinology & Metabolism Clinics of North America 12/1999; 28(4):883-900. · 3.41 Impact Factor
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ABSTRACT: The pathogenesis of excess cardiovascular risk in type 1 diabetes is unclear. LDL cholesterol is only weakly predictive, and its concentration is often normal in type 1 diabetes. We therefore examined whether markers of LDL oxidation such as antibodies to oxidized LDL (Ab-OxLDL) and LDL-containing immune complexes, rather than LDL concentration, were predictive of coronary artery disease (CAD) in type 1 diabetes. This nested case-control study from an epidemiologic cohort study included 49 incident cases of myocardial infarction (MI), angina, or CAD death and 49 age-, sex-, and duration-matched control subjects. Ab-OxLDL was measured by enzyme immunoassay and the apolipoprotein B (ApoB) content of immune complexes (ApoB-IC) precipitated by polyethylene glycol by immunoelectrophoresis in baseline stored samples. Ab-OxLDL was inversely, and ApoB-IC directly, related to subsequent CAD. In multivariate analyses, Ab-OxLDL remained a significant independent predictor along with previously recognized predictors, hypertension and Beck depression score. In conclusion, oxidation of LDL and the immune response it elicits may play a role in predicting the development of CAD in type 1 diabetes and explain at least some of the enhanced CAD risk in type I diabetes.
Diabetes 08/1999; 48(7):1454-8. · 8.29 Impact Factor
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ABSTRACT: Serum leptin levels reflect the amount of body fat. However, several reports suggest that insulin may also regulate serum leptin levels. This study was aimed at testing whether leptin levels are low in newly diagnosed patients with type 1 diabetes and increase after institution of insulin therapy. Nineteen children with new-onset type 1 diabetes were studied. Serum leptin levels were measured at presentation before insulin therapy was initiated (day 0), 1 day after insulin therapy (day 1), 3-5 days after insulin therapy (day 3-5), and at 3 months of follow-up (3 months). The control group consisted of 19 healthy children matched for age and body mass index. On day 0 leptin levels were lower in the patients compared with those in controls (3.3 +/- 0.2 vs. 6.2 +/- 0.9 ng/mL; P < 0.005). After insulin therapy, leptin levels increased significantly by day 1 without significant weight change and became comparable to control values by days 3-5. Before insulin therapy, leptin did not correlate with weight, body mass index, or hemoglobin A1c. After insulin therapy, leptin levels on days 3-5 correlated with insulin dose (r = 0.43; P = 0.03). The results of this study demonstrate that children with new-onset type 1 diabetes have low leptin levels before insulin therapy. Leptin levels increase within 24 h of insulin therapy and become comparable to nondiabetic levels by 3-5 days. This rapid increase in leptin after 24 h of insulinization is independent of changes in body weight and is postulated to be due to a stimulatory effect of insulin on leptin production, nutritional replenishment, or both factors together.
Journal of Clinical Endocrinology & Metabolism 05/1999; 84(5):1524-6. · 6.50 Impact Factor
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Journal of Pediatrics 05/1999; 134(4):392-4. · 4.11 Impact Factor
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ABSTRACT: Several groups have published results from clinical studies supporting the involvement of anti-modified LDL antibodies as risk factors for the initiation or progression of cardiovascular disease. However, the data published so far are judged inconclusive because of several contradictory observations concerning the correlation between clinical evidence of arteriosclerosis and the levels of antibodies to oxidized LDL (oxLDL Ab). We have previously reported that oxLDL Ab exist both in free form and as antigen-antibody complexes (LDL-IC) in patients with insulin-dependent diabetes mellitus (IDDM). The presence of LDL-IC in IDDM patients has important implications: it may interfere with the assay of oxLDL antibodies and the levels of LDL-IC may correlate better with the development of arteriosclerosis than the levels of free oxLDL antibodies. To clarify these questions baseline samples collected from 49 IDDM patients, who subsequently developed coronary artery disease (CAD) during an 8-year follow-up period, were compared to baseline samples from 49 age-, sex-, and duration-matched control IDDM subjects who remained free of clinical CAD during an identical follow-up period. The levels of free oxLDL antibody were significantly lower in the patients who developed CAD. The same patients had significantly higher concentrations of total cholesterol, apolipoprotein B, and IgA in immune complex-enriched polyethylene glycol (PEG) precipitates. The concentration of IgG was also higher in PEG precipitates from patients who developed CAD, but did not reach statistical significance. This indicates that patients who develop CAD had higher levels of circulating LDL-IC, a fact that could not be deduced from the measurement of free oxLDL antibody concentrations. A linear regression analysis of the correlation between the concentrations of total cholesterol in PEG precipitates, taken as a surrogate measurement of PEG-precipitated oxLDL-IC, and the concentration of free oxLDL antibody in serum showed a statistically significant negative correlation (r = -0.229, P = 0. 024). Our results support the conclusion that oxLDL-IC may be a risk factor for the development of macrovascular disease in IDDM patients. We also have demonstrated that circulating oxLDL-IC interfere with the assay of free oxLDL antibodies.
Clinical Immunology 03/1999; 90(2):165-72. · 4.05 Impact Factor
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ABSTRACT: To examine whether a potential marker for type 2 diabetes (family history) is related to CAD in type 1 diabetic subjects. The two major types of primary diabetes, type 1 and type 2, are both associated with an increased risk of developing coronary artery disease (CAD). However, the etiology and associated risk factors may differ by type of diabetes. In type 2 diabetes, CAD is likely to be linked with the insulin resistance associated with the type 2 "process," while CAD in type 1 diabetes has, so far, been more closely linked to renal disease. Because the etiologies of type 1 and type 2 diabetes are different, it is possible that some CAD in type 1 diabetes may be related to the coexistence of type 2 diabetes susceptibility (i.e., insulin resistance).
We evaluated the interrelationships between family history of type 2 diabetes (age at onset > 30 years, no insulin for 1st year) and presence of CAD in a cohort of childhood-onset type 1 diabetic subjects using the Pittsburgh Epidemiology of Diabetes Complications study (n = 658).
A first-degree family history of type 2 diabetes was reported in 112 subjects, and CAD was present in 119 subjects. Those subjects reporting a family history of type 2 diabetes were significantly older, had a longer duration of type 1 diabetes, had higher triglyceride and LDL cholesterol levels, and had a borderline significantly increased Beck depression inventory. Sex differences in CAD risk factors were also noted. Using logistic regression analysis, the odds ratio (95% CI) for the presence of CAD in association with a family history of NIDDM was 1.89 (1.27-2.84). The odds ratio (95% CI) after adjusting for disease duration, triglycerides, hypertension, Beck depression, and nephropathy status was 1.45 (0.87-2.28).
We conclude that a family history of type 2 diabetes is a risk factor for CAD in type 1 diabetic subjects. This supports the concept that insulin resistance may contribute to development of CAD in type 1 diabetes.
Diabetes Care 05/1998; 21(4):610-4. · 8.09 Impact Factor
